Management of Autoimmune Encephalitis
Immediate First-Line Immunotherapy
Start high-dose corticosteroids immediately once infection is ruled out, as this is the most commonly used first-line therapy selected by 84% of expert clinicians for general presentations of autoimmune encephalitis. 1
First-Line Treatment Selection Algorithm
Intravenous methylprednisolone (IVMP) is the preferred initial agent, dosed at 1-2 mg/kg/day or as pulse therapy at 1g daily for 3-5 days in severe cases 2, 3, 4
Switch to IVIG (0.4 g/kg/day for 5 days, total 2 g/kg) if the patient is agitated/combative, has bleeding disorders, or cannot tolerate central line placement 3, 4
Switch to plasma exchange (5-10 sessions every other day) if the patient has severe hyponatremia, high thromboembolic risk, or associated brain/spinal demyelination 3, 4
Combine steroids with IVIG or PLEX from the outset in patients with severe initial presentations (decreased consciousness, status epilepticus, or severe autonomic dysfunction) 4
Critical Timing Consideration
Do not wait for antibody test results before initiating treatment—antibody panels often take weeks to return, and delay in immunotherapy worsens outcomes and mortality 2, 4
Treatment should begin as soon as infectious causes are reasonably excluded through CSF analysis and appropriate cultures 2
Escalation to Second-Line Therapy
Add rituximab if there is no meaningful clinical, radiological, or electrophysiological improvement after 2-4 weeks of optimized first-line therapy. 3, 4
Second-Line Agent Selection
Rituximab is the preferred second-line agent, chosen by 80% of experts for cases with unknown antibodies, and is particularly effective for antibody-mediated autoimmune encephalitis 1, 3, 4
Cyclophosphamide should be used instead when cell-mediated autoimmunity is suspected (particularly with intracellular/onconeuronal antibodies like anti-Hu, anti-Ma2) 3, 4
Only 15% of experts add second-line agents to all patients upfront; most (50%) wait until failure of more than one first-line agent 1
Supportive Care Requirements
Seizure Management
- Initiate appropriate antiepileptic medications for seizure control, as seizures including new-onset refractory status epilepticus (NORSE) commonly occur 2, 4
Autonomic Dysfunction
- Monitor and aggressively treat blood pressure and heart rate fluctuations 4
- Consider temporary pacemaker placement for severe dysrhythmias 4
Hyponatremia Management
- Implement fluid restriction for syndrome of inappropriate antidiuretic hormone secretion (SIADH) 4
- Avoid rapid correction as this can worsen neurological status 4
Intracranial Pressure Monitoring
- Monitor intracranial pressure in cases with massive inflammation and brain edema 4
Malignancy Screening
Perform contrast-enhanced CT of chest, abdomen, and pelvis at diagnosis to screen for underlying malignancy, as paraneoplastic causes must be identified and treated 4
Continue cancer surveillance for 4 years in patients with neuronal surface antibodies (49% of experts) or limbic encephalitis (46% of experts) 5
Screening duration can be shorter (2 years) in non-limbic seronegative cases 5
Long-Term Immunosuppression
Maintenance Therapy Indications
Initiate maintenance immunosuppression after a second relapse in patients with neuronal surface antibodies (70% of experts agree) or seronegative autoimmune encephalitis (61% of experts agree) 5
Maintenance therapy is less commonly used after first episode unless there are high-risk features 5
Maintenance Agent Selection
Rituximab is the most popular maintenance therapy, chosen by 46% of experts 5
Oral prednisone taper is the most popular bridging therapy (38% of experts) between acute and maintenance phases 5
Special Populations
Immune Checkpoint Inhibitor-Related Cases
Permanently discontinue the checkpoint inhibitor immediately in cases of immune checkpoint inhibitor-related autoimmune encephalitis 3, 4
Common Pitfalls to Avoid
Never delay treatment waiting for antibody results—commercial panels are limited, many cases remain seronegative, and early treatment is the strongest predictor of favorable outcomes 1, 2, 4
Do not exclude autoimmune encephalitis based on normal CSF studies—testing for neuronal autoantibodies should still be performed with high clinical suspicion 2
Collect blood samples for antibody testing before administering IVIG or PLEX to avoid false-negative results 2
Do not miss paraneoplastic causes—failure to screen for underlying malignancy can result in treatment failure despite aggressive immunosuppression 4
Patients with onconeuronal antibodies (anti-Hu, anti-Ma2, anti-CRMP5) typically respond poorly to immunotherapy alone and require tumor removal for meaningful improvement 5